Selection of pacing sites to enhance cardiac performance

ABSTRACT

Systems and methods for selection of electrodes and related pacing configuration parameters used to pace a heart chamber are described. A change in the hemodynamic state of a patient is detected. Responsive to the detected change, a distribution of an electrical, mechanical, or electromechanical parameter related to contractile function of a heart chamber with respect to locations of multiple electrodes disposed within the heart chamber is determined. A pacing output configuration, including one or more electrodes of the multiple electrodes, is selected and the heart chamber is paced using the selected pacing output configuration.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/479,877 filed on Jun. 30, 2006, which is incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates generally to cardiac pacing therapy, andmore specifically, to selection of electrodes and related pacingconfiguration parameters used to pace a heart chamber.

BACKGROUND OF THE INVENTION

When functioning normally, the heart produces rhythmic contractions andis capable of pumping blood throughout the body. The heart hasspecialized conduction pathways in both the atria and the ventriclesthat enable the rapid conduction of excitation impulses (i.e.depolarizations) from the SA node throughout the myocardium. Thesespecialized conduction pathways conduct the depolarizations from the SAnode to the atrial myocardium, to the atrio-ventricular node, and to theventricular myocardium to produce a coordinated contraction of bothatria and both ventricles.

The conduction pathways synchronize the contractions of the musclefibers of each chamber as well as the contraction of each atrium orventricle with the opposite atrium or ventricle. Without thesynchronization afforded by the normally functioning specializedconduction pathways, the heart's pumping efficiency is greatlydiminished. Patients who exhibit pathology of these conduction pathwayscan suffer compromised cardiac output.

Cardiac rhythm management devices have been developed that providepacing stimulation to one or more heart chambers in an attempt toimprove the rhythm and coordination of atrial and/or ventricularcontractions. Cardiac rhythm management devices typically includecircuitry to sense signals from the heart and a pulse generator forproviding electrical stimulation to the heart. Leads extending into thepatient's heart chamber and/or into veins of the heart are coupled toelectrodes that sense the heart's electrical signals and for deliveringstimulation to the heart in accordance with various therapies fortreating cardiac arrhythmias.

Pacemakers are cardiac rhythm management devices that deliver a seriesof low energy pace pulses timed to assist the heart in producing acontractile rhythm that maintains cardiac pumping efficiency. Pacepulses may be intermittent or continuous, depending on the needs of thepatient. There exist a number of categories of pacemaker devices, withvarious modes for sensing and pacing one or more heart chambers.

Pacing therapy has been used in the treatment of congestive heartfailure (CHF). CHF causes diminished pumping power of the heart,resulting in the inability to deliver enough blood to meet the demandsof peripheral tissues. CHF may cause weakness, loss of breath, and buildup of fluids in the lungs and other body tissues. CHF may affect theleft heart, right heart or both sides of the heart. For example, CHF mayoccur when deterioration of the muscles of the heart produce anenlargement of the heart and/or reduced contractility. The reducedcontractility decreases the cardiac output of blood and may result in anincreased heart rate. In some cases, CHF is caused by unsynchronizedcontractions of the left and right heart chambers, denoted atrial orventricular dysynchrony. Particularly when the left or right ventriclesare affected, the unsynchronized contractions can significantly decreasethe pumping efficiency of the heart.

Pacing therapy to promote synchronization of heart chamber contractionsto improve cardiac function is generally referred to as cardiacresynchronization therapy (CRT). Some cardiac pacemakers are capable ofdelivering CRT by pacing multiple heart chambers. Pacing pulses aredelivered to the heart chambers in a sequence that causes the heartchambers to contract in synchrony, increasing the pumping power of theheart and delivering more blood to the peripheral tissues of the body.In the case of dysynchrony of right and left ventricular contractions, abiventricular pacing therapy may pace one or both ventricles. Bi-atrialpacing or pacing of all four heart chambers may alternatively be used.

SUMMARY OF THE INVENTION

The present invention is directed to systems and methods for selectionof electrodes and related pacing configuration parameters used to pace aheart chamber. One embodiment involves a method, implementable by acardiac therapy system, for delivering pacing therapy to a heart. Achange in the hemodynamic state of a patient is detected. Responsive tothe detected change, a distribution of an electrical, mechanical, orelectromechanical parameter related to contractile function of a heartchamber with respect to locations of multiple electrodes disposed withinthe heart chamber is determined. A pacing output configuration,including one or more electrodes of the multiple electrodes, is selectedand the heart chamber is paced using the selected pacing outputconfiguration.

The change in the hemodynamic state may include, for example, a chronicchange or an acute change. In various implementations, the hemodynamicstate chamber detected may include a change in at least one of heartrate, activity, posture, respiration rate, minute ventilation, cardiacoutput, blood chemistry, cardiac dysynchrony, pressure, blood oxygenconcentration, impedance, heart rate variability, heart sounds, AVinterval, and QRS width. For example, detecting the change inhemodynamic state may involve detecting increased or decreased metabolicdemand.

Determination of the parameter distribution may involve determining oneor more electrical cardiac parameters such as depolarizationcharacteristics including depolarization delays, atrioventricular timingintervals, depolarization amplitude, depolarization-repolarizationintervals, depolarization thresholds, and/or other depolarizationcharacteristics. Determination of the parameter distribution may involvedetermining one or more mechanical cardiac parameters such ashypertrophy, wall stress, wall strain, peak displacement, peak velocity,peak strain, minimum displacement, minimum velocity, minimum strain,time to peak or minimum displacements, velocities, and strain, amongother mechanical parameters. Determination of the parameter distributionmay involve determining one or more electromechanical cardiac parameterssuch as interval from electrical depolarization time to peak strain, orother combinations of the electrical and mechanical properties.

The selection of the electrode configuration may involve selecting oneor more electrodes disposed at locations having longer depolarizationdelays relative to depolarization delays of other locations. In oneimplementation, one or more previously selected electrodes and one ormore additional electrodes may be selected, where the one or morepreviously selected electrodes are associated with the longestdepolarization delays and the one or more additional electrodesassociated with the next longest depolarization delays. The heartchamber may be paced by delivering pacing pulses to the selectedelectrodes in a timed sequence based on the parameter distribution.

In certain embodiments, information related to the change in hemodynamicstatus, parameter distribution, and pacing output configuration isstored. A lookup table may be generated based on the stored information.A subsequent pacing output configuration may be selected basedinformation stored in the lookup table. The stored information may bedisplayed to a health care professional or used for analysis at a latertime, for example.

Another embodiment of the invention is directed to a cardiac therapysystem. The therapy system includes multiple electrodes respectivelypositionable at multiple locations within a heart chamber. One or moresensors and associated detection circuitry are configured to detect achange in a patient's hemodynamic state. A processor is configured todetermine a distribution of a parameter related to the contractilefunction of the heart chamber with respect to the multiple electrodelocations responsive to a detected change in the hemodynamic state.Selection circuitry is used to select one or more electrodes of themultiple electrodes based on the measured parameter. A pulse generatordelivers pacing therapy to the heart chamber via the selectedelectrodes.

The paced chamber may include a ventricle or an atrium, or multiplechambers may be paced by the cardiac therapy system via selectablepacing output configurations for each paced chamber.

The one or more sensors and associated circuitry configured to detectthe change in hemodynamic state may include, for example, sensors andcircuitry configured to sense and detect physiological parametersrelated to hemodynamic state including transthoracic impedance,respiration rate, minute ventilation, heart rate, cardiac dysynchrony,activity, posture, blood chemistry, O2 saturation, heart sounds, wallstress, wall strain, hypertrophy, inter-electrode impedance, electricaldelays (PR interval, AV interval, QRS width, etc.), activity, cardiacchamber pressure, cardiac output, temperature, heart rate variability,depolarization amplitudes, depolarization timing, and/or otherphysiological parameters.

In some implementations, the selection circuitry is configured todetermine a timing sequence for pacing pulses delivered to the one ormore electrodes based on the parameter distribution. In theseimplementations, the pulse generator is configured to deliver the pacingpulses to the one or more electrodes according to the timing sequence.In some implementations, the selection circuitry is configured to selectamplitudes for pacing pulses delivered to the one or more electrodesbased on the parameter distribution. In these implementations, the pulsegenerator is configured to deliver the pacing pulses to the one or moreelectrodes at the selected amplitudes.

In certain embodiments, at least one of the detection circuitry, theprocessor, and the selection circuitry comprises a patient-externalcomponent. In other embodiments, the detection circuitry, processor, andselection circuitry are fully implantable.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a patient-implantable device that may be used inconjunction with selection of pacing output configuration for deliveryof stimulation pulses in accordance with embodiments of the invention;

FIG. 2 is a flow graph illustrating a process for pulse outputconfiguration in accordance with embodiments of the invention;

FIG. 3 is a block diagram of circuitry used for selection of the pulseoutput configuration in accordance with embodiments of the invention;

FIG. 4 is a flow diagram illustrating a process of for determiningpacing output configuration triggered by an indication of an acutechange in hemodynamic status in accordance with embodiments of theinvention; and

FIG. 5 is a flow graph of a method useful for determining the pacingoutput configuration when a chronic change in hemodynamic status isindicated in accordance with embodiments of the invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings, which form a part hereof, and inwhich is shown by way of illustration, various embodiments in which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Systems, devices or methods according to the present invention mayinclude one or more of the features, structures, methods, orcombinations thereof described hereinbelow. For example, a device orsystem may be implemented to include one or more of the advantageousfeatures and/or processes described below. It is intended that suchdevice or system need not include all of the features described herein,but may be implemented to include selected features that provide foruseful structures and/or functionality. Such a device or system may beimplemented to provide a variety of therapeutic or diagnostic functions.

A cardiac therapy device may deliver electrical stimulation pulses toone or more electrodes disposed within the heart chamber and/orotherwise electrically coupled to the myocardium to initiatecontractions of the chamber. Embodiments of the invention are directedto systems and methods for selection of one or more electrodes disposedwithin a heart chamber for application of pacing pulses. The pacingpulses may be delivered via the selected electrodes in accordance withtiming and/or amplitude/pulse waveform output configurations thatprovide improved contractile function of the chamber.

The therapy device 100 illustrated in FIG. 1 is an embodiment of apatient-implantable device that may be used in conjunction withselection of electrodes, timing sequences, and/or amplitude/pulse width(collectively referred to herein as pacing output configuration) fordelivery of stimulation pulses. The therapy device 100 includes cardiacrhythm management (CRM) circuitry enclosed within an implantable housing101. The CRM circuitry is electrically coupled to an intracardiac leadsystem 110.

Portions of the intracardiac lead system 110 are inserted into thepatient's heart. The lead system 110 includes cardiac pace/senseelectrodes 151-156 positioned in, on, or about one or more heartchambers for sensing electrical signals from the patient's heart and/ordelivering pacing pulses to the heart. The intracardiac sense/paceelectrodes 151-156, such as those illustrated in FIG. 1, may be used tosense and/or pace one or more chambers of the heart, including the leftventricle, the right ventricle, the left atrium and/or the right atrium.The lead system 110 includes one or more defibrillation electrodes 141,142 for delivering defibrillation/cardioversion shocks to the heart.

The left ventricular lead 105 incorporates multiple electrodes 154 a-154d positioned at various locations within, on or about the leftventricle. Stimulating the ventricle at multiple locations or at asingle selected location may provide for increased cardiac output in apatients suffering from CHF. In accordance with various embodimentsdescribed herein, one or more of the electrodes 154 a-154 d are selectedfor pacing the left ventricle. In other embodiments, leads havingmultiple pacing electrodes positioned at multiple locations within achamber, such as the one illustrated by the left ventricular lead 105 ofFIG. 1, may be implanted within any or all of the heart chambers. A setof electrodes positioned within one or more chambers may be selected.Electrical stimulation pulses may be delivered to the chambers via theselected electrodes according to a timing sequence and outputconfiguration that enhances cardiac function.

Portions of the housing 101 of the implantable device 100 may optionallyserve as one or multiple can or indifferent electrodes. The housing 101is illustrated as incorporating a header 189 that may be configured tofacilitate removable attachment between one or more leads and thehousing 101. The housing 101 of the therapy device 100 may include oneor more can electrodes 181 b, 181 c. The header 189 of the therapydevice 100 may include one or more indifferent electrodes 181 a. Thehousing 101 and/or header 189 may include any number of electrodespositioned anywhere in or on the housing 101 and/or header 189.

The cardiac electrodes and/or other sensors disposed within or on thehousing 101 or lead system 110 of the therapy device 100 may producesignals used for detection and/or measurement of various physiologicalparameters, such as transthoracic impedance, respiration rate, minuteventilation, heart rate, cardiac dysynchrony, activity, posture, bloodchemistry, O2 saturation, heart sounds, wall stress, wall strain,hypertrophy, inter-electrode impedance, electrical delays (PR interval,AV interval, QRS width, etc.), activity, cardiac chamber pressure,cardiac output, temperature, heart rate variability, depolarizationamplitudes, depolarization timing, and/or other physiologicalparameters.

For example, in some configurations, the implantable device 100 mayincorporate one or more transthoracic impedance sensors that may be usedto acquire the patient's respiratory waveform, and/or to acquire otherrespiratory-related information. The transthoracic impedance sensor mayinclude, for example, one or more intracardiac electrodes 141, 142,151-156 positioned in one or more chambers of the heart. Theintracardiac electrodes 141, 142, 151-156 may be coupled to impedancedrive/sense circuitry positioned within the housing 101 of the therapydevice 100. Information from the transthoracic impedance sensor may beused to adapt the rate of pacing to correspond to the patient's activityor metabolic need.

Communications circuitry is disposed within the housing 101 forfacilitating communication between the CRM circuitry and apatient-external device, such as an external programmer or advancedpatient management (APM) system. The communications circuitry may alsofacilitate unidirectional or bidirectional communication with one ormore implanted, external, cutaneous, or subcutaneous physiologic ornon-physiologic sensors, patient-input devices and/or informationsystems.

In certain embodiments, the therapy device 100 may include circuitry fordetecting and treating cardiac tachyarrhythmia via defibrillationtherapy and/or anti-tachyarrhythmia pacing (ATP). Configurationsproviding defibrillation capability may make use of defibrillation coils141, 142 for delivering high energy shocks to the heart to terminate ormitigate tachyarrhythmia.

In some embodiments, the implantable therapy device 100 may includecircuitry for selection of pacing electrode(s), timing sequence, and/oramplitude or pulse waveform output configurations (referred tocollectively herein as the pacing output configuration) to be appliedvia one or multiple electrodes within one or multiple heart chambers. Inother embodiments, the therapy device 100 may transfer sensed or derivedinformation relevant to pacing output configuration to apatient-external device. Following download of the implantably sensed orderived information, selection of the pacing output configuration may bemade by the patient-external device or may be made by a clinician usinginformation provided via the patient-external device.

Pacing output configuration involves selection of the site or sites ofpacing within a heart chamber and/or the temporal sequence of the pacingpulses delivered to the multiple sites, and may also optionally involveselection of particular pulse characteristics (e.g., amplitude,duration, anodal/cathodal polarity, and waveshape) used for the pacingpulses. Selection of the pacing output configuration is particularlydesirable for optimal application of cardiac resynchronization therapy.Congestive heart failure, long term pacing, ischemia, myocardialinfarction and/or other factors can produce non-uniformities in theelectrical, mechanical or electromechanical properties of themyocardium. These non-uniformities can cause a heart chamber to contractin an uncoordinated manner resulting in inefficient pumping action. Thelocation of the pacing site or sites and/or other properties of thepacing output configuration affects the spread of the depolarizationexcitation which in part determines the manner in which the chambercontracts. In a pacemaker equipped with multiple pacing electrodesrespectively disposed at multiple pacing sites within a heart chamber,the ability to select one or more electrodes, temporal sequence, and/orpulse waveform characteristics for delivery of pacing can be usedenhance the contractile function of the heart chamber.

Multi-site pacemakers, such as illustrated herein, are capable ofdelivering pacing pulses to multiple sites of the atria and/orventricles during a cardiac cycle. Certain patients may benefit fromactivation of parts of a heart chamber, such as a ventricle, atdifferent times in order to distribute the pumping load and/ordepolarization sequence to different areas of the ventricle. Amulti-site pacemaker has the capability of switching the output ofpacing pulses between selected electrodes or groups of electrodes withina heart chamber during different cardiac cycles. For example, the pacingpulses may be delivered to the heart chamber at specified locations andat specified times during the cardiac cycle to enhance the synchrony ofthe contraction. Amplitude, pulse duration, anodal/cathodal polarityand/or waveshape of the pacing pulses may also be altered to enhancepumping function.

FIG. 2 is a flow graph illustrating an approach for pulse outputconfiguration in accordance with one approach. In this example,optimization of the pulse output configuration is triggered based on achange the patient's hemodynamic status. According to one approach, asensor or other device is used to detect 210 a change that indicates thepatient's hemodynamic status has changed. The change in hemodynamicstatus may be indicated based on acute or chronic changes. For example,an acute or chronic change in hemodynamic status may be indicated bychanges in heart rate, respiration rate, minute ventilation, tidalvolume, posture, O2 saturation, cardiac dysynchrony, medication,progression of CHF, fluid retention, dyspnea, disordered breathing,weight gain, decreased level of activity, posture, posture correlated toperiods of sleep, duration of pacing therapy, disease status, ischemia,myocardial infarction, and/or other changes indicative of a change inhemodynamic status of the patient.

A detected change in the patient's hemodynamic status may indicate aneed to adjust the pulse output configuration to achieve optimal pacingtherapy for the patient's changed status. Responsive to the detectedchange in hemodynamic status, the contractile function of at least oneheart chamber is assessed 220 by determining the distribution of anelectrical, mechanical or electromechanical parameter related tocontractile function of the chamber with respect to locations ofmultiple electrodes disposed within the heart chamber. The pacing outputconfiguration, including selection 230 of one or more electrodes, isdetermined based on the distribution of the parameter. The heart chamberis paced 240 using the selected electrodes.

In one example, change in hemodynamic status involves an increase ordecrease in metabolic demand as indicated by a change in heart rate. Inthis example, the parameter related to contractile function comprisesthe timing of the spread of a depolarization wavefront within a heartchamber. Depolarization delays from site to site within a heart chambermay change as a function of heart rate. Thus, an electrode or electrodespreviously selected for pacing at a baseline heart rate may no longerproduce an optimal contraction of the heart chamber at an elevated heartrate due to changes in the depolarization delays across the heartchamber when the heart rate is elevated. The distribution ofdepolarization delays at the multiple electrode sites is determined. Thepulse output configuration is re-optimized for the elevated rate byaltering the electrode or electrodes selected for pacing, such as byselecting one or more electrodes associated with the longestdepolarization delays as the pacing electrodes.

Optimization of the pacing output configuration may be used to preventor reverse the effects of undesirable remodeling due to ischemia ormyocardial infarction (MI). Changes in cardiac ischemia or MI conditionsare associated with changes in the distribution of wall stress within aheart chamber. In one example, detection of changes in cardiac ischemiaor MI conditions indicates a change in hemodynamic status. Responsive tothis change, electrodes for pacing may be selected so that a minimalamount of stress is placed on an affected region. In otherconfigurations, the electrodes may be selected to produce a uniformstress distribution, or to pre-excite a stressed region of themyocardium relative to other regions.

FIG. 3 is a block diagram of circuitry used for selection of the pulseoutput configuration in accordance with embodiments of the invention.Multiple cardiac electrodes 345 are disposed at multiple locationswithin a heart chamber. One or more sensors 310 are configured to sensephysiological factors indicative of a patient's hemodynamic status.Responsive to a detected change in hemodynamic status, determination ofthe distribution of one or more parameters related to the contractilefunction of the heart is triggered. The parameter distribution mayindicate that a change in the pacing output configuration would bebeneficial. In various implementations, the hemodynamic statusindicators used to trigger determination of the pacing outputconfiguration may be selectable by the therapy device or programmable bya clinician.

The parameter distribution processor 330 assesses the distribution of anelectrical, mechanical or electromechanical parameter related tocontractile function of the heart chamber. For example, the parameterdistribution processor 330, in conjunction with the cardiac electrodes345, may assess the distribution of an electrical cardiac parameter ateach of the electrode locations. For example, electrical cardiacparameters may include depolarization characteristics such asdepolarization delays, atrioventricular timing intervals, depolarizationamplitude, depolarization-repolarization intervals, depolarizationthresholds, and/or other depolarization characteristics. The parameterdistribution processor 330, may assess the distribution of mechanicalcardiac parameters such as hypertrophy, wall stress, wall strain, peakdisplacement, peak velocity, peak strain, minimum displacement, minimumvelocity, minimum strain, time to peak or minimum displacements,velocities, and strain, among other mechanical parameters. The parameterdistribution processor 330 may assess the distribution ofelectromechanical cardiac parameters such as interval from electricaldepolarization time to peak strain, or other combinations of theelectrical and mechanical properties.

In one embodiment, depolarization delays may be measured at eachelectrode site during an intrinsic systolic contraction. Thedistribution of depolarization delays can be determined by measuring thetiming of R-wave peaks detected via cardiac electrograms sensed at eachof the cardiac electrodes during the contraction.

In accordance with some embodiments, cardiac sensing circuitry 340 mayinclude individual sense amplifiers and peak detectors for eachelectrode in the ventricle. In other embodiments, a bipolar sensingtechnique may be used to reduce the number of sense amplifiers and/orother signal processing circuitry required to detect the depolarizationdelay distribution. Measurement of the distribution of depolarizationdelays in a heart chamber may be accomplished using the techniquesdescribed in commonly owned U.S. Patent Publications 2004/0098056 or2004/0102812 which are incorporated herein by reference.

After measurement of the distribution of the parameter related tocontractile function, selection circuitry 325 selects an appropriatepacing output configuration. According to one aspect, the selectioncircuitry 325 may select an electrode corresponding to a pacing sitehaving a longest depolarization delay or may select a number ofelectrodes for pacing in a pattern or sequence based on their respectiveconduction delays. In some configurations, the electrode associated withthe longest delay may be paced first, the electrode associated with thesecond longest delay may be paced next, and so forth.

As described above, one way of selecting a pacing site forresynchronization therapy is to measure the depolarization delays ofpotential pacing sites. One or more sites that are demonstrated to beexcited later in the contraction sequence may then be selected as pacingsites. Pacing the latest activated site, or pacing multiple sites in asequence corresponding to their respective conduction delays may providea more coordinated contraction.

Changes in the presence of areas of ischemia, scar tissue or infarctionmay cause changes in wall stress within a cardiac chamber.Resynchronization pacing may be applied to the stressed myocardialregions so that the stress at the high stress regions is decreased, suchas by reducing the preload and afterload to which the region issubjected.

In various embodiments, re-optimization of the pacing outputconfiguration may be triggered by detection of an increased heart rate,ischemia, or MI, for example. The parameter distribution processor 330assesses the distribution of wall stress in the heart chamber. Forexample, distribution of wall stress may be accomplished by measuringthe action potential duration at each electrode during systole.Measurement of the action potential durations may be implemented bysensing an electrogram at each electrode during a cardiac cycle andmeasuring the time between a depolarization and a repolarization at eachelectrode.

In one embodiment, determination of wall stress distribution andreoptimization of the pacing output configuration may be based on thephenomena of mechanical alternans. When oscillations in pulse pressureare detected in a patient, referred to as pulse alternans, it isgenerally interpreted as a sign of left ventricular dysfunction.Localized alternations in local wall stress, as revealed by alternationsin the action potential duration may similarly indicate that the site issubject to increased stress. The stress distribution at the electrodesites may be identified by detecting the degree of oscillation in themeasured action potential duration at the electrode sites.

Sites that are most stressed may be identified as those sites havingsmallest action potential duration and/or the greatest amount ofoscillation in the action potential duration. The selection circuitry325 may determine the pacing output configuration by selecting a siteexhibiting a high stress relative to the stress at other sites as thepacing electrode site. In another approach, the selection circuitry 325selects a number of sites of pacing, wherein the sites are paced in asequence based on the relative amount of wall stress detected at each ofthe sites. Sites exhibiting relatively higher levels of wall stress maybe pre-excited with respect to sites exhibiting relatively lower levelsof wall stress. Techniques for assessing wall stress are described incommonly owned U.S. Pat. No. 6,965,797 which is incorporated herein byreference.

In some embodiments, detection of a change in hemodynamic status maytrigger an assessment of the distribution of hypertrophy exhibited by acardiac chamber. Hypertrophy refers to a thickening of the myocardialtissue. Congestive heart failure may cause an increase of the diastolicfilling pressure of the ventricles which increases the ventricularpreload (i.e., the degree to which the ventricles are stretched by thevolume of blood in the ventricles at the end of diastole). CHF can be atleast partially compensated by this mechanism. However, when theventricles are stretched due to increased preload over a period of time,the ventricles become dilated. The enlargement of the ventricular volumecauses increased ventricular wall stress at a given systolic pressure.This phenomenon stimulates hypertrophy of the ventricular myocardium.Sustained stresses causing hypertrophy may cause death of the cardiacmuscle cells, wall thinning and further deterioration in cardiacfunction. Thus, it is desirable to identify hypertrophic areas and applypacing in such a way that the stressed areas area unloaded.

A depolarization wavefront propagating through a hypertrophiedmyocardial region results in a greater potential being measured by asensing electrode due to the increased muscle mass of the hypertrophiedregion. During depolarization, the electrogram signal measured at anelectrode disposed near a relatively hypertrophied region has a greateramplitude than a signal measured from an electrode near anunhypertrophied region. In one embodiment, the distribution ofhypertrophic myocardial tissue in the heart chamber is determined.Hypertrophy at each electrode site may be determined by the parameterdistribution processor 330 based on the amplitude of electrogram signalmeasured at each electrode.

The pacing output configuration may be determined based on the relativeamplitudes of electrogram signals detected at each of the electrodesites. The pacing output configuration is selected by the selectioncircuitry 325 so that hypertrophic regions are mechanically unloadedduring pacing.

In some embodiments, changes in hypertrophy may be determined bymeasuring electrical impedance between the electrodes or throughsonomicrometry measurements. For example, changes in hypertrophy of acardiac chamber may be measured via an array of implanted piezoelectricsonomicrometer transducers disposed within the chamber.

After selection of the pacing output configuration by any of the methodsdescribed above, pacing is delivered by the pacing therapy circuitry 335via the selected electrode(s).

In some embodiments, the parameter distribution processor 330 and pacingoutput selection circuitry 325 may include functionality to initiatedetermination of the pacing output configuration based on a plurality ofhemodynamic status indicators. Signals associated with the patient'shemodynamic status may be generated by multiple sensors. If the value ofone or more of the signals changes beyond a threshold level, then adetermination of the pacing output configuration may be triggered. Insome implementations, determination of the pacing output configurationis based on a relationship between the values of two or more sensorsignals. For example, an increase in disordered breathing with aconcurrent decrease in activity may indicate a worsening of CHF. Thepacing output configuration may be re-optimized if an increase indisordered breathing above a predetermined threshold is detectedconcurrently with a decrease in activity below a predeterminedthreshold.

In some configurations, the parameter distribution processor 330 iscapable of determining more than one electromechanical parameterdistribution. One or more distributions used to configure the pacingoutput configuration may be selected by the device or programmed by aclinician. In one configuration, the one or more electromechanicalparameter distributions used to configure the pacing output may berelated to the hemodynamic status indicators. For example, if aparticular hemodynamic status indicator that is more closely related tothe likelihood of wall stress triggers the pacing output configurationprocess, then wall stress may be selected as the electromechanicalparameter distribution used for pacing output configuration.

In another configuration, the one or more electromechanical parameterdistributions used to configure the pacing output may be selected basedon the goals of the pacing output configuration. The goals of the pacingoutput configuration may be determined by the device or programmed by aclinician. For example, if a goal of the pacing output configuration isto reduce ventricular dysynchrony, then the pacing output configurationmay be based on the distribution of depolarization delay. If a goal ofthe pacing output configuration is to reduce remodeling due to wallstress, then the pacing output configuration may be based on thedistribution of wall stress. Using the wall stress distribution toselect the pacing output configuration to reduce remodeling may be moreeffective than using depolarization delay distribution becausemyocardial regions that are subjected to the highest levels ofmechanical stress during contractions may not always correspond to thesites with the largest conduction delay due to the presence of scartissue or areas of infarction.

Circuitry for determining the distribution of an electromechanicalparameter related to contractile function and to select a pacing outputconfiguration may be provided in a therapy device. In one embodiment,the processes included within the dashed line 301 of FIG. 3 may beprovided by an implantable therapy device such as the implantable deviceillustrated in FIG. 1. Such a device may include a power supply (notshown) and memory 320 for storing program instructions and/or data. Invarious configurations, the memory may be used to store informationincluding information about the change in hemodynamic condition, theparameter distribution assessment, and/or the pacing outputconfiguration. The information stored in the memory may be used tocreate a lookup table for future reference that may be used to selectthe pacing output configuration if a subsequent similar change in thehemodynamic condition is observed. In addition, the stored informationmay be used to provide a log of events for display or analysis at alater time. The device also includes communications circuitry 315 forcommunicating with a patient-external device 305 such as a programmer oradvanced patient management system.

In some configurations, the implantable device may provide some of thefunctionality for selection of pacing output configuration, and apatient-external device may provide some of the functionality. Forexample, in one embodiment, the patient-external device communicateswith the implantable device over a telemetry link and receives eitherraw data, markers corresponding to particular sensed events, and/ormeasurements of timing intervals or other signal characteristics asdetermined by the implantable device. The external device may thendetermine the electromechanical parameter distribution and computeoptimal settings for the pacing output configuration which are eithertransmitted to the implantable device for immediate reprogramming, orpresented to a clinician operating the external device as arecommendation. Alternatively, the external device may present the rawdata, markers and/or measurements to the clinician who then programs theimplantable device in accordance with an algorithm.

In some implementations, an advanced patient management (APM) systemremotely monitors the patient's hemodynamic status. If a change inhemodynamic status is detected, the APM system signals the implantabledevice to initiate determination of the electromechanical parameterdistribution. In some scenarios selection of the pacing outputconfiguration may be performed by the implantable device. In otherscenarios, the APM system may perform the selection. Various therapeuticand/or diagnostic medical devices coupled to the APM system can providesensing capability for use in detecting the patient's hemodynamic statevia a multi-sensor approach. The APM system may be coupled to a varietyof patient-external and patient-implantable devices, each deviceincorporating a set of sensors which are remotely accessible to the APMsystem.

A user interface may be coupled to the APM allowing a physician toremotely monitor cardiac functions, as well as other patient conditions.The user interface may be used by the clinician to access informationavailable via the APM. The clinician may also enter information via theuser interface for setting up the pacing output configurationfunctionality. For example, the clinician may select particular sensors,hemodynamic status indicators, indicator levels or sensitivities, and/orelectromechanical parameters. Methods, structures, and/or techniquesdescribed herein, may incorporate various APM related methodologies,including features described in one or more of the following references:U.S. Pat. Nos. 6,221,011; 6,270,457; 6,277,072; 6,280,380; 6,312,378;6,336,903; 6,358,203; 6,368,284; 6,398,728; and 6,440,066, which arehereby incorporated herein by reference.

FIG. 4 is a flow diagram illustrating a process of for determiningpacing output configuration in accordance with an embodiment of theinvention. In this embodiment, the system senses for 410 indicators ofan acute change in hemodynamic status. For example, an acute change inhomodynamic status may include be detected based on changes in posture,O2 level, activity, heart rate, respiration rate, minute ventilation,and/or other factors. In one particular example, an increase inhemodynamic status comprises a change in metabolic demand. If anincrease in demand is detected 420, such a change in the hemodynamicdemand indicator beyond a baseline level, the system determines 430 thedistribution of a depolarization delays at multiple electrode sites. Ifone or more electrode sites other than those used in the previous(baseline) pulse output configuration have 440 the longestdepolarization delays, the system switches 490 the pacing outputconfiguration to include the one or more sites having the longest delay.

If the previous pulse output configuration includes 440 the one or moreelectrode sites having the longest depolarization delays, the systemswitches 450 the pacing output configuration to recruit an additionalone or more electrodes, such as those one or more electrodes having thesecond longest depolarization delays.

If the system detects 460 a decrease in hemodynamic demand, such as backto the baseline level, then one of two optional processes may beimplemented. According to a first optional process (Option A) the systemswitches 470 the pacing output configuration to the previously usedbaseline configuration. According to a second optional process (OptionB) the system determines 480 the distribution of the depolarizationdelays at the multiple sites for the decreased demand condition. Thepulse output configuration is selected 490 to include one or moreelectrode sites having the largest depolarization delays. The change inhemodynamic condition that prompted the pacing configuration change, themeasurement of the parameter distribution, and/or the final electrodeconfiguration used for pacing may be stored 451, 471 either in theimplantable device or patient-external device. The information storedmay be used as a lookup table for subsequent selection of a pacingconfiguration. Additionally, or alternatively, the stored informationmay be used to provide a log of events that may be reviewed and/oranalyzed at a later time.

FIG. 5 is a flow graph of a method useful for determining the pacingoutput configuration when a chronic change in hemodynamic status isdetected. Chronic changes in hemodynamic status may be indicated by aprogression of CHF symptoms, such as increased breathing disorders,elevated posture during sleeping, changes in left ventricular pressures,detection of myocardial infarction, and/or other long-term changes inhemodynamic status. If chronic changes are detected 510, the systemre-optimizes the pacing output configuration to provide enhanced pumpingfunction. The system determines 520 the distribution of depolarizationdelays (or other electromechanical parameters) at multiple electrodesites. If one or more new sites have 530 larger delays than thepreviously used sites, then the new sites are selected 550 for use inthe pulse output configuration. The previously used sites may or may notbe excluded from the pulse output configuration. If the previously usedsites still have 530 the largest delays, the previously used sites areselected 540 along with one or more additional sites which have thesecond largest delays. The condition that prompted the pacingconfiguration change, the measurement of the parameter distribution,and/or the final electrode configuration used for pacing may be stored541.

Various modifications and additions can be made to the preferredembodiments discussed hereinabove without departing from the scope ofthe present invention. Accordingly, the scope of the present inventionshould not be limited by the particular embodiments described above, butshould be defined only by the claims set forth below and equivalentsthereof.

What is claimed is:
 1. A cardiac therapy system, comprising: multipleelectrodes positionable in, on, or about different locations of a leftventricle of a heart; one or more sensors configured to detect a changein hemodynamic state of a patient; a controller operatively coupled tothe one or more sensors for determining a change in a hemodynamic stateof a patient, and in responsive to determining the change in hemodynamicstate, the controller is configured to: determine a parameter related tocontractile function of a heart chamber with respect to each of thelocations of the multiple electrodes; determine a distribution of theparameter with respect to the locations of the multiple electrodes;select a subset of electrodes of the multiple electrodes based, at leastin part, on the determined parameter distribution; and a pulse generatoroperatively coupled to the controller, the pulse generator configured topace the heart chamber using the selected one or more electrodes.
 2. Thecardiac therapy system of claim 1, wherein the parameter comprises adepolarization delay.
 3. The cardiac therapy system of claim 2, whereinthe controller determines a depolarization delay at each of thelocations of the multiple electrodes.
 4. The cardiac therapy system ofclaim 3, wherein the controller selects the subset of electrodes basedon the distribution of depolarization delays.
 5. The cardiac therapysystem of claim 4, wherein the controller selects the subset ofelectrodes based on the longest depolarization delays in thedistribution of depolarization delays.
 6. The cardiac therapy system ofclaim 1, wherein the one or more sensors comprise a chemical sensor forsensing a change in the patient's blood chemistry that is indicative ofa change in the hemodynamic state of the patient.
 7. The cardiac therapysystem of claim 1, wherein the one or more sensors comprise a patientactivity sensor for sensing a change in the patient's activity that isindicative of a change in the hemodynamic state of the patient.
 8. Thecardiac therapy system of claim 1, wherein the one or more sensorscomprise a respiration sensor for sensing a change in the patient'srespiration that is indicative of a change in the hemodynamic state ofthe patient.
 9. The cardiac therapy system of claim 1, wherein the oneor more sensors comprise a cardiac electrogram sensor for sensing achange in the patient's cardiac electrogram that is indicative of achange in the hemodynamic state of the patient.
 10. The cardiac therapysystem of claim 1, wherein: the controller is configured to determine atiming sequence for pacing pulses to be delivered to the selected one ormore electrodes based on the parameter distribution; and the pulsegenerator is configured to deliver the pacing pulses to the selected oneor more electrodes according to the timing sequence.
 11. The cardiactherapy system of claim 1, wherein: the controller is configured todetermine amplitudes for pacing pulses to be delivered to the selectedone or more electrodes based on the parameter distribution; and thepulse generator is configured to deliver the pacing pulses to theselected one or more electrodes according at the determined amplitudes.12. The cardiac therapy system of claim 1, wherein at least one of theone or more sensors comprises a patient-external component.
 13. Thecardiac therapy system of claim 1, wherein the controller comprises apatient-external component.
 14. A cardiac therapy system, comprising:multiple electrodes respectively positionable at multiple locations in,on, or about a left ventricle of a heart; one or more sensors configuredto detect a chronic and acute change in a patient's hemodynamic state; acontroller operatively coupled to the one or more sensors fordetermining when a chronic change and an acute change in the patient'shemodynamic state occurs, the controller is further configured to: inresponse to determining a chronic change in the patient's hemodynamicstate, select a first pacing output configuration including a firstsubset of electrodes of the multiple electrodes; in response todetermining an acute change in the patient's hemodynamic state, select asecond pacing output configuration including a second subset ofelectrodes of the multiple electrodes, wherein the second subset ofelectrodes is different from the first subset of electrodes; and a pulsegenerator configured to deliver a cardiac resynchronization therapy tothe left ventricle using the selected first or second pacing outputconfiguration.
 15. The cardiac therapy system of claim 14, wherein theone or more sensors comprises one or more of a chemical sensor, apatient activity sensor, a respiration sensor, and a cardiac electrogramsensor.
 16. The cardiac therapy system of claim 14, wherein in responseto determining a chronic change in the patient's hemodynamic state, thecontroller is further configured to: determine a depolarization delaywith respect to each of the multiple electrodes; determine adistribution of the depolarization delays; select the first subset ofelectrodes of the multiple electrodes based, at least in part, on thedetermined distribution.
 17. The cardiac therapy system of claim 14,wherein in response to determining an acute change in the patient'shemodynamic state, the controller is further configured to: determine adepolarization delay with respect to each of the multiple electrodes;determine a distribution of the depolarization delays; select the secondsubset of electrodes of the multiple electrodes based, at least in part,on the determined distribution.
 18. A cardiac therapy system,comprising: multiple electrodes of a multiple electrode leadrespectively positionable at multiple locations in, on, or about a leftventricle of a heart; one or more sensors configured to detect a chronicand acute change in a patient's hemodynamic state; a controlleroperatively coupled to the one or more sensors for determining when achronic change and an acute change in the patient's hemodynamic stateoccurs, the controller is further configured to: in response todetermining a chronic change in the patient's hemodynamic state, selecta first pacing output configuration including a first subset ofelectrodes of the multiple electrodes; in response to determining anacute change in the patient's hemodynamic state, select a second pacingoutput configuration including a second subset of electrodes of themultiple electrodes, wherein the second subset of electrodes isdifferent from the first subset of electrodes; the controller is furtherconfigured to: determine a depolarization delay with respect to each ofthe multiple electrodes; determine a distribution of the depolarizationdelays; select the first subset of electrodes of the multiple electrodesbased, at least in part, on the determined distribution; select thesecond subset of electrodes of the multiple electrodes based, at leastin part, on the determined distribution; and a pulse generatorconfigured to deliver a cardiac resynchronization therapy to the leftventricle using the selected first or second pacing outputconfiguration.
 19. The cardiac therapy system of claim 18, wherein: thecontroller is further configured to determine a timing sequence forpacing pulses to be delivered to the first subset of electrodes of thefirst pacing output configuration based, at least in part, on theparameter distribution; and the pulse generator is configured to deliverthe pacing pulses to the first subset of electrodes of the first pacingoutput configuration according to the timing sequence.
 20. The cardiactherapy system of claim 19, wherein: the controller is furtherconfigured to determine a timing sequence for pacing pulses to bedelivered to the second subset of electrodes of the second pacing outputconfiguration based, at least in part, on the parameter distribution;and the pulse generator is configured to deliver the pacing pulses tothe second subset of electrodes of the second pacing outputconfiguration according to the timing sequence.